Improved Detection of Molecular Markers of Atherosclerotic Plaques Using Sub-Millimeter PET Imaging

Since atherosclerotic plaques are small and sparse, their non-invasive detection via PET imaging requires both highly specific radiotracers as well as imaging systems with high sensitivity and resolution. This study aimed to assess the targeting and biodistribution of a novel fluorine-18 anti-VCAM-1...

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Bibliographic Details
Main Authors: Jessica Bridoux, Sara Neyt, Pieterjan Debie, Benedicte Descamps, Nick Devoogdt, Frederik Cleeren, Guy Bormans, Alexis Broisat, Vicky Caveliers, Catarina Xavier, Christian Vanhove, Sophie Hernot
Format: Article
Language:English
Published: MDPI AG 2020-04-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/25/8/1838
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Summary:Since atherosclerotic plaques are small and sparse, their non-invasive detection via PET imaging requires both highly specific radiotracers as well as imaging systems with high sensitivity and resolution. This study aimed to assess the targeting and biodistribution of a novel fluorine-18 anti-VCAM-1 Nanobody (Nb), and to investigate whether sub-millimetre resolution PET imaging could improve detectability of plaques in mice. The anti-VCAM-1 Nb functionalised with the novel restrained complexing agent (RESCA) chelator was labelled with [<sup>18</sup>F]AlF with a high radiochemical yield (>75%) and radiochemical purity (>99%). Subsequently, [<sup>18</sup>F]AlF(RESCA)-cAbVCAM1-5 was injected in ApoE<sup>−/−</sup> mice, or co-injected with excess of unlabelled Nb (control group). Mice were imaged sequentially using a cross-over design on two different commercially available PET/CT systems and finally sacrificed for ex vivo analysis. Both the PET/CT images and ex vivo data showed specific uptake of [<sup>18</sup>F]AlF(RESCA)-cAbVCAM1-5 in atherosclerotic lesions. Non-specific bone uptake was also noticeable, most probably due to in vivo defluorination. Image analysis yielded higher target-to-heart and target-to-brain ratios with the β-CUBE (MOLECUBES) PET scanner, demonstrating that preclinical detection of atherosclerotic lesions could be improved using the latest PET technology.
ISSN:1420-3049